Response of autophagy and ubiquitin-proteasome pathways to ultra-endurance running

AIMS: Modulation of ubiquitin-proteasome pathway (UPP), autophagy-lysosomal pathway (ALP) and mitochondrial remodelling were assessed by measuring protein markers during ultra-endurance exercise in human skeletal muscle. METHODS: Eleven male ultra-endurance athletes ran for 24 hours on a treadmill. Biopsies were taken from the vastus lateralis muscle two hours before starting and immediately after finishing exercise. RESULTS: The phosphorylation state of Akt (-74%), FoxO3a (-49%), mTOR Ser2448 (-32%) and 4E-BP1 (-34%) decreased significantly whereas AMPK phosphorylation state increased by 247%. Proteasome β2 subunit activity and MuRF1 protein level increased by 95% and 55%, respectively. LC3bII and the form of ATG12 conjugated to ATG5 increased by 554% and 36%, respectively. The mitochondrial fission marker phospho-DRP1 increased by 110% whereas the fusion marker Mfn1 and the mitophagy markers Parkin and PINK1 remained unchanged. CONCLUSION: These results fit well with a coordinated regulation of ALP and UPP triggered by FoxO3 and AMPK during ultra-endurance exercise.